How would you approach a patient with metastatic ER/PR+, HER2- breast cancer with linear leptomeningeal enhancement on MRI but negative CSF protein and cytology?

First, it is important to note that the sensitivity of CSF cytology depends on both the number of LPs and the volume of LP. For example, one LP has a sensitivity of only ~70%, while doing more than 3 LPs takes the sensitivity up to 98%. Similarly, withdrawing at least 10 ml of CSF improves sensitivity. (Glantz et al., PMID 9477107). Emerging technologies, such as CSF tumor cell detection or protein biomarkers, will likely improve this sensitivity but are not yet generally available. Therefore, I would make sure there have been at least 2 large volume LPs before calling CSF cytology negative.

If the protein and cytology are persistently negative, then my treatment recommendations are based on symptoms, recognizing that no treatment has been p...